Prenatal THC exposure interferes with the neurodevelopmental role of endocannabinoid signaling

Abstract

The contribution of the endocannabinoid (ECB) system to brain development has been the subject of intense research. Studies have addressed the neurodevelopmental consequences of ECB signaling manipulation by using different genetic paradigms. Other studies used administration of exogenous cannabinoids (plant-derived THC and synthetic agonists) during different developmental windows to investigate the consequences of prenatal cannabinoid exposure (PCE). Here we focus on PCE to THC, as a CB1 receptor targeting molecule. Other cannabinoids have been less investigated and would not be discussed herein. Stem cell-derived methodologies, hiPSC-derived neuronal differentiation and three-dimensional cerebral organoids constitute powerful approaches to investigate the neurodevelopmental role and function of the ECB system, and the impact of PCE in the human brain. The consequences of PCE are due to its interference with CB1 receptor signaling in different developing neural cell populations, which control proliferation, differentiation, migration, and maturation responsible for neuronal network and brain development.